PROJECT SUMMARY The overall goal of Core C (Animal Use and Development Core) is to support the development and use of the animal models utilized within this Program Project Grant (PPG). The guiding principals for Core C are efficient planning and utilization of animals, standardization of processing and diagnoses, reliability of service and consistent evaluation of animal models and being a cost center for all animal costs. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The Core is housed and coordinated in the Department of Veterinary Biosciences. Dr. Stefan Niewiesk, Core Director has been (Co-) Director of the Animal Core since 2004 and is an active collaborator with all Project Leaders for the PPG. He is certified in Veterinary Microbiology and as a Laboratory Animal Medicine Veterinarian (European). Dr. Thomas Rosol (Co-investigator), who is certified by the American College of Veterinary Pathology, will provide pathological evaluations for the Core. The overall theme of the PPG is to analyze how infection with HTLV-1 induces proliferation of CD4 T cells, how viral proteins and integration sites influence and maintain transformation and how the tumor cells interact with their microenvironment. After acute infection, HTLV-1 persists in the organism, eventually leading to oligoclonal and finally monoclonal proliferation and transformation of CD4+ T cells. After integration of the virus (Project 2; Kvaratskhelia), tumorigenesis is driven by the viral proteins Tax and Hbz (Projects 1 and 4; Green and Ratner), which includes altered patterns of expression of regulatory proteins. These leukemic cells spread throughout the organism and cause osteolysis and often hypercalcemia (Project 3; Weilbaecher and Rosol). All projects will use mice with a human immune system (HIS mice) as a model for adult T cell leukemia which has been established by Core C using a molecular clone of HTLV-1.